Dual inhibition of key proliferation signaling pathways in triple-negative breast cancer cells by a novel derivative of Taiwanin A

Yueh Hsiung Kuo, En Pei Isabel Chiang, Che Yi Chao, Raymond L. Rodriguez, Pei Yu Chou, Shu Yao Tsai, Man Hui Pai, Feng Yao Tang

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

The treatment of breast cancer cells obtained by blocking the aberrant activation of the proliferation signaling pathways PI3K/Akt/mTOR and MEK/ERK has received considerable attention in recent years. Previous studies showed that Taiwanin A inhibited the proliferation of several types of cancer cells. In this study, we report that 3,4-bis-3,4,5-Trimethoxybenzylidene- dihydrofuran (BTMB), a novel derivative of Taiwanin A, significantly inhibited the proliferation of triple-negative breast cancer (TNBC) cells both in vitro and in vivo. The results show that BTMB inhibited the proliferation of human TNBC cells by the induction of cell-cycle arrest and apoptosis in a dose-dependent fashion. BTMB inhibited the expression of b-catenin, cdc2 and the cell-cycle regulatory proteins, cyclin A, cyclin D1, and cyclin E. The mechanism of action was associated with the suppression of cell survival signaling through inactivation of the Akt and ERK1/2 signaling pathways. Moreover, BTMB induced cell apoptosis through an increase in the expression of BAX, cleaved caspase-3, and cleaved PARP. Moreover, BTMB inhibited TNBC cell colony formation and sensitized TNBC cells to cisplatin, a chemotherapeutic drug. In a TNBC mouse xenograft model, BTMB significantly inhibited the growth of mammary carcinomas through decreased expression of cyclin D1. BTMB was shown to significantly suppress the growth of mammary carcinoma and therefore to have potential as an anticancer therapeutic agent.

Original languageEnglish
Pages (from-to)480-493
Number of pages14
JournalMolecular Cancer Therapeutics
Volume16
Issue number3
DOIs
Publication statusPublished - Mar 1 2017

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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